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Prospective Comparison of 99mTc-MDP Scintigraphy,
Combined 18F-NaF and 18F-FDG PET/CT, and Whole-Body
MRI in Patients with Breast and Prostate Cancer
Ryogo Minamimoto1,2, Andreas Loening3, Mehran Jamali1,2, Amir Barkhodari1, Camila Mosci1, Tatianie Jackson1,
Piotr Obara3, Valentina Taviani3, Sanjiv Sam Gambhir1,2, Shreyas Vasanawala3, and Andrei Iagaru1
1Division
of Nuclear Medicine and Molecular Imaging, Department of Radiology, Stanford University, Stanford, California;
Imaging Program at Stanford, Department of Radiology, Stanford University, Stanford, California; and 3Radiological
Sciences Laboratory, Department of Radiology, Stanford University, Stanford, California
2Molecular
We prospectively evaluated the use of combined 18F-NaF/18FFDG PET/CT in patients with breast and prostate cancer and compared the results with those for 99mTc-MDP bone scintigraphy and
whole-body MRI. Methods: Thirty patients (15 women with breast
cancer and 15 men with prostate cancer) referred for standard-ofcare bone scintigraphy were prospectively enrolled in this study.
18F-NaF/18F-FDG PET/CT and whole-body MRI were performed
after bone scintigraphy. The whole-body MRI protocol consisted
of both unenhanced and contrast-enhanced sequences. Lesions
detected with each test were tabulated, and the results were compared. Results: For extraskeletal lesions, 18F-NaF/18F-FDG PET/CT
and whole-body MRI had no statistically significant differences in
sensitivity (92.9% vs. 92.9%, P 5 1.00), positive predictive value
(81.3% vs. 86.7%, P 5 0.68), or accuracy (76.5% vs. 82.4%, P 5
0.56). However, 18F-NaF/18F-FDG PET/CT showed significantly higher
sensitivity and accuracy than whole-body MRI (96.2% vs. 81.4%,
P , 0.001, 89.8% vs. 74.7%, P 5 0.01) and bone scintigraphy
(96.2% vs. 64.6%, P , 0.001, 89.8% vs. 65.9%, P , 0.001) for
the detection of skeletal lesions. Overall, 18F-NaF/18F-FDG PET/CT
showed higher sensitivity and accuracy than whole-body MRI
(95.7% vs. 83.3%, P , 0.002, 87.6% vs. 76.0%, P , 0.02) but
not statistically significantly so when compared with a combination
of whole-body MRI and bone scintigraphy (95.7% vs. 91.6%, P 5
0.17, 87.6% vs. 83.0%, P 5 0.53). 18F-NaF/18F-FDG PET/CT showed
no significant difference from a combination of 18F-NaF/18F-FDG PET/
CT and whole-body MRI. No statistically significant differences in
positive predictive value were noted among the 3 examinations.
Conclusion: 18F-NaF/18F-FDG PET/CT is superior to whole-body
MRI and 99mTc-MDP scintigraphy for evaluation of skeletal disease extent. Further, 18F-NaF/18F-FDG PET/CT and whole-body
MRI detected extraskeletal disease that may change the management of these patients. 18F-NaF/18F-FDG PET/CT provides diagnostic ability similar to that of a combination of whole-body MRI
and bone scintigraphy in patients with breast and prostate cancer. Larger cohorts are needed to confirm these preliminary findings, ideally using the newly introduced simultaneous PET/MRI
scanners.
Received Jun. 23, 2015; revision accepted Sep. 10, 2015.
For correspondence or reprints contact: Andrei Iagaru, Division of Nuclear
Medicine and Molecular Imaging, Department of Radiology, Stanford
University, 300 Pasteur Dr., H2200, Stanford, CA 94305.
E-mail: aiagaru@stanford.edu
Published online Sep. 24, 2015.
COPYRIGHT © 2015 by the Society of Nuclear Medicine and Molecular
Imaging, Inc.
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Key Words: 99mTc-MDP; 18F-NaF;
prostate cancer; breast cancer
18F-FDG;
whole-body MRI;
J Nucl Med 2015; 56:1862–1868
DOI: 10.2967/jnumed.115.162610
I
n patients with breast cancer, the National Comprehensive Cancer Network guidelines recommend diagnostic CT of the chest and
abdomen (and pelvis if needed), 99mTc-methylene diphosphonate
(99mTc-MDP) bone scintigraphy or 18F-NaF PET/CT, and optional
18F-FDG PET/CT (1). Although 18F-FDG PET/CT has great potential for identifying locally advanced and metastatic lesions (2), the
guidelines recommend it only if the results of conventional imaging
are equivocal or suggestive. Bone scintigraphy or 18F-NaF PET/CT
may be avoided when 18F-FDG PET/CT has already identified skeletal metastasis, according to the same guidelines. However, the sensitivity of 18F-FDG PET/CT for detection of osteoblastic lesions is
limited in breast cancer (3). 18F-FDG PET/CT has not been recommended by the National Comprehensive Cancer Network guidelines
for prostate cancer (4), although there are reports suggesting its
usefulness in detecting locally recurrent or metastatic disease, assessing the extent of metabolically active, castration-resistant disease
(5). 18F-FDG uptake in prostate cancer lesions is an independent
prognostic factor and provides information complementary to that
from bone scintigraphy (6). 18F-NaF PET/CT has greater sensitivity
than bone scintigraphy and therefore has been recommended for
evaluation of skeletal metastases in patients with prostate cancer
(4). Skeletal metastases from prostate cancer are usually osteoblastic
but may also have mixed or osteolytic features (7). 18F-NaF PET/CT
is superior to bone scintigraphy for skeletal lesion detection in prostate and breast cancer (8–11).
Whole-body MRI with diffusion-weighted imaging is as sensitive
as 18F-FDG PET/CT but less specific for the detection of locoregional or metastatic breast cancer (12). Whole-body diffusionweighted imaging has higher specificity but lower sensitivity than
18F-NaF PET/CT in prostate cancer (13).
The combined administration of 18F-NaF and 18F-FDG (18F2/
18F-FDG) in a single PET/CT scan for cancer detection has been
advocated for detecting both extraskeletal and skeletal lesions
(14,15), and a prospective international multicenter trial showed
promising results (16).
NUCLEAR MEDICINE • Vol. 56 • No. 12 • December 2015
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We now evaluated the performance of 18F2/18F-FDG PET/CT for
the detection of extraskeletal and skeletal lesions in a selected population of patients with breast and prostate cancer and compared it
with whole-body MRI and bone scintigraphy.
MATERIALS AND METHODS
Patient Population
The local Institutional Review Board and Cancer Center Scientific
Review Committee approved this study, and all participants gave
written informed consent. To be included, patients had to be older than
18 y at the time of recruitment; have a diagnosis of breast cancer with
an initial clinical stage of III or more; have a diagnosis of prostate
cancer with an initial clinical stage of II or more or a serum prostatespecific antigen level of 10 or more; have been referred for evaluation
of possible skeletal metastases with bone scintigraphy or have shown
the presence of skeletal metastases on bone scintigraphy; and be able
to remain still for the duration of the imaging procedure. Exclusion
criteria were limited to pregnancy/nursing and the presence of metallic
implants (contraindicated for whole-body MRI).
Between November 2012 and July 2014, 15 women (mean age 6
SD, 54.1 6 12.6 y; range, 34–76 y) with pathologically proven breast
cancer and 15 men (mean age 6 SD, 68.3 6 9.4 y; range, 52–84 y)
with pathologically proven prostate cancer were included in this study.
Bone scintigraphy was performed first and was followed by the
18F2/18F-FDG PET/CT and whole-body MRI scans. The interval was
15.4 6 8.0 d between bone scintigraphy and 18F2/18F-FDG PET/CT
and 2.5 6 3.9 d between 18F2/18F-FDG PET/CT and whole-body MRI.
At the time of bone scintigraphy, the prostate-specific antigen levels for
prostate cancer patients, and the pathologic result for expression of
estrogen receptor, progesterone receptor, and human epidermal receptor
2 for breast cancer patients, were recorded.
Bone Scintigraphy Protocol
No patient preparation was required. Pregnancy was excluded by
history. The intravenous dose of 99mTc-MDP was 935.6 6 42.1 MBq
(range, 777.0–1,017.5 MBq). The patients were asked to return to the
clinic 3 h after 99mTc-MDP administration, during which time they
were encouraged to hydrate and void. On returning, planar images of
the whole body and spot views of the thorax and pelvis in anterior and
posterior views were acquired. Per routine clinical practice, additional
spot (planar or oblique) views of the body were obtained if deemed
necessary. The images were acquired using dual-head g-cameras
(Infinia Hawkeye 4 [GE Healthcare] or Skylight [Philips Healthcare]).
All images were interpreted using a dedicated Xeleris workstation
version 2.0551; GE Healthcare). SPECT or SPECT/CT images were
not acquired.
18F−/18F-FDG
PET/CT Protocol
The patients were scanned on Discovery 600 or 690 scanners (GE
Healthcare). There were only small (,10%) differences in SUV measurements between scanners based on data from phantom studies.
Patients were asked to fast for 6 h before injection of 18F2/18F-FDG.
For the 18F2/18F-FDG PET/CT scans, the 2 radiotracers were delivered
from the local cyclotron facilities in separate syringes and intravenously
administered sequentially, without delay. For all PET/CT scans, totalbody (vertex to toes) PET/CT images were obtained in 3-dimensional
mode, with the patients’ arms at their sides. The PET images were
reconstructed with a standard iterative algorithm (ordered-subset expectation maximization, 2 iterative steps and 32 subsets for Discovery 600
and 2 iterative steps and 24 subsets for Discovery 690), as recommended by the manufacturer.
The dosages of 18F2/18F-FDG were 567.0 6 30.0 MBq (range, 506.9–
625.3 MBq), of which 18F-FDG included 370.1 6 24.7 MBq (range,
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321.9–414.4 MBq) and 18F-NaF included 189.8 6 16.1 MBq (range,
155.4–218.3 MBq). The time from injection to the start of the 18F2/18FFDG PET/CT scans was 70.1 6 12.2 min (range, 50–104 min).
Whole-Body MRI Protocols and Image Reconstruction
Whole-body MRI studies were acquired on a 750W 3-T scanner (GE
Healthcare) using a whole-body coil. Unenhanced sequences included
coronal T1-weighted fast spin echo imaging (repetition time/echo time
[TR/TE], ;700/8 ms; echo train length, 6; bandwidth, 54 kHz; flip
angle, 90; slice thickness, 8 mm; 0.5 excitations; field of view, 44
cm; matrix, 448 · 256), coronal short-t inversion recovery imaging
(TR/TE, 9,500/45 ms; inversion time, 190 ms; echo train length, 20;
bandwidth, 62.5 kHz; slice thickness, 8 mm; field of view, 44 cm; 0.5
excitations; matrix, 384 · 224) with station 2 (lungs) acquired in
a breath hold (TR/TE, 3,000/45 ms; inversion time, 190 ms; slice thickness, 8 mm; field of view, 44 cm; 0.5 excitations; matrix, 384 · 192),
and axial echo planar diffusion-weighted imaging (TR/TE, 4,300/55
ms; slice thickness, 8 mm; slice spacing, 8 mm; b value, 50 and 500
ms; field of view, 40 cm; 4 excitations; matrix, 80 · 128). After injection of a weight-based dose of gadofosveset (Ablavar; Lantheus
Medical Imaging), enhanced sequences were obtained consisting of
axial 3-dimensional spoiled gradient recalled echo imaging with 2-point
Dixon fat/water separation (flip angle, 15; TR/TE, 4.5/1.1 and 2.3 ms;
slice thickness, 3 mm; field of view, 44 cm; matrix, 320 · 256).
Image Analysis
The bone scintigraphy and 18F2/18F-FDG PET/CT scans were
interpreted by 2 board-certified nuclear medicine physicians in randomized order, with masking of the diagnosis and the results of other
imaging studies. Two board-certified radiologists performed the
whole-body MRI interpretation also in randomized order. Agreement
was reached by consensus. A direct comparison for each detected
lesion was performed among the 3 scans by one of the investigators.
For the interpretation of the scans, visual analysis was used instead of
semiquantitative analysis (i.e., SUV cutoffs). For the 18F2/18F-FDG
PET/CT scans, areas of focally increased 18F2/18F-FDG uptake were
recorded as malignant unless a benign etiology (e.g., degenerative
changes or hemangioma) for this uptake was identified at the same
location on the corresponding CT images. The CT component of PET/CT
was used to determine whether bone lesions identified on PET had an
osteoblastic or osteolytic appearance. For whole-body MRI, all sequences
were assessed concurrently, with the radiologist’s clinical experience
used for detecting lesions. Visual conspicuity against background on
the diffusion-weighted images and the presence of an anatomically corresponding abnormality on the fast spoiled gradient-echo and short-t
inversion recovery images were the criteria for detecting a lesion on
whole-body MRI. Diagnostic accuracy was evaluated by comparing the
bone scintigraphy, 18F2/18F-FDG PET/CT, and whole-body MRI results
with the final diagnoses as confirmed by histologic evaluation, clinical
follow-up, or other imaging studies. We also evaluated the diagnostic
ability of combining the results from bone scintigraphy and whole-body
MRI and from 18F2/18F-FDG PET/CT and whole-body MRI.
Statistical Analysis
Differences in sensitivity and accuracy were compared by the
McNemar test. The x2 test for independence was performed to compare the positive predictive value (PPV). The statistical difference of
specificity and negative predictive value (NPV) were not tested in this
study because of the bias in the population. P values of less than 0.05
were considered statistically significant.
RESULTS
The clinical characteristics of the enrolled patients are shown
in Table 1. Two patients with prostate cancer could not complete
BREAST AND PROSTATE CANCER • Minamimoto et al.
1863
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TABLE 1
Clinical Characteristics of Patient Population
Female
(breast
cancer)
Male
(prostate
cancer)
Number of patients
15
15
Mean age ± SD (y)
54.1 ± 12.6
68.3 ± 9.4
II
0
5
III
8
4
IV
7
6
3
1
12
14
Characteristic
Clinical stage at
initial diagnosis
Indication for bone
scintigraphy
Initial treatment
strategy
Subsequent
treatment strategy
Prostate-specific
antigen
Mean ± SD
8.6 ± 10.1
Range
0.1–30.3
Pathologic findings
ER1, PR1, Her2−
5
—
ER1, PR1, Her21
4
—
ER1, PR−, Her21
2
—
ER−, PR−, Her2−
2
—
ER−, PR−, Her21
2
—
ER 5 estrogen receptor; PR 5 progesterone receptor; Her2 5
human epidermal receptor 2.
the whole-body MRI scan and were therefore excluded from the
analysis.
Pathology reports (13% of the patients) or clinical follow-up
(87% of the patients) were available as the gold standard for the
results. Suspected malignant lesions were identified by 18F2/18FFDG PET/CT in 20 of 30 participants (breast cancer: n 5 12,
prostate cancer: n 5 8), by bone scintigraphy in 16 of 30 participants (breast cancer: n 5 10, prostate cancer: n 5 6), by wholebody MRI in 19 of 28 participants (breast cancer: n 5 11, prostate
cancer: n 5 8), by a combination of whole-body MRI and bone
scintigraphy in 19 of 28 participants (breast cancer: n 5 11, prostate
cancer: n 5 8), and by a combination of whole-body MRI and
18F2/18F-FDG PET/CT in 20 of 28 participants (breast cancer: n 5
11, prostate cancer: n 5 9). Typical examples are shown in Figures 1–3.
Patient-Based Analysis
Table 2 shows the results of the per-patient analysis. Overestimation of clinical staging by 18F2/18F-FDG PET/CT occurred in 2
participants. One was a case of false-positive findings in the pelvic
skeleton in a patient with prostate cancer, and the other was a case
of false-positive findings in an axillary lymph node in a patient
with breast cancer. Overestimation of clinical stage by whole-body
MRI occurred in the patient who had a false-positive axillary
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lymph node on 18F2/18F-FDG PET/CT. Bone scintigraphy failed
to identify skeletal lesion in 2 patients, but these were demonstrated on the corresponding whole-body MRI.
Lesion-Based Analysis
Total Lesions. In total 98 lesions (extraskeletal: n 5 16; skeletal:
n 5 82) were identified by 18F2/18F-FDG PET/CT in 30 participants, 79 lesions (extraskeletal: n 5 15; skeletal: n 5 64) were
identified by whole-body MRI in 28 participants, 53 lesions (all
skeletal) were identified by bone scintigraphy in 30 participants,
85 lesions (extraskeletal: n 5 15, skeletal: n 5 70) were identified
by a combination of whole-body MRI and bone scintigraphy in 28
participants, and 96 lesions (extraskeletal: n 5 17; skeletal: n 5 79)
were identified by a combination of 18F2/18F-FDG PET/CT and
whole-body MRI in 28 participants.
The per-lesion sensitivity, specificity, PPV, NPV, and accuracy of
18F2/18F-FDG PET/CT, whole-body MRI, bone scintigraphy, and
the combination of whole-body MRI and bone scintigraphy are
shown in Table 3. For extraskeletal lesions, 18F2/18F-FDG PET/
CT and whole-body MRI had no statistically significant differences
in sensitivity (P 5 1.00), PPV (P 5 0.32), or accuracy (P 5 0.56).
However, 18F2/18F-FDG PET/CT showed significantly higher sensitivity and accuracy than whole-body MRI (P , 0.001, P , 0.02)
and bone scintigraphy (P , 0.001, P , 0.001) for the detection of
skeletal lesions. Overall, 18F2/18F-FDG PET/CT showed higher
sensitivity and accuracy than whole-body MRI (P , 0.002, P ,
0.02) but not statistically significantly so when compared with
a combination of whole-body MRI and bone scintigraphy (P 5
0.17, P 5 0.52). 18F2/18F-FDG PET/CT showed no difference from
a combination of 18F2/18F-FDG PET/CT and whole-body MRI. No
statistically significant differences in PPV were noted among the 3
examinations.
Skeletal Lesions. Among 82 skeletal lesions identified on the
CT component of PET/CT, 6 were osteolytic; all 6 occurred in
patients with breast cancer. The other 76 lesions were osteoblastic.
The per-lesion sensitivity, specificity, PPV, NPV, and accuracy of
18F2/18F-FDG PET/CT, whole-body MRI, bone scintigraphy, and
the combination of whole-body MRI and bone scintigraphy for the
osteolytic and osteoblastic skeletal lesions are shown in Tables 3
(prostate and breast cancer) and 4 (breast cancer). For osteolytic
lesions, 18F2/18F-FDG PET/CT and whole-body MRI showed
higher sensitivity than bone scintigraphy, but no statistical significance was achieved given the small number of lesions.
For osteoblastic lesions, 18F2/18F-FDG PET/CT had significantly higher sensitivity (P , 0.001) and accuracy (P , 0.001)
than bone scintigraphy. 18F2/18F-FDG PET/CT had no statistically
significant differences in sensitivity (P 5 0.61) or PPV (P 5 0.43)
but had higher accuracy than whole-body MRI (P , 0.05).
18F2/18F-FDG PET/CT showed no statistically significant difference from a combination of whole-body MRI and bone scintigraphy (P 5 0.32, P 5 0.13) but was less sensitive than a combination
of 18F2/18F-FDG PET/CT and whole-body MRI (P 5 0.01).
Breast Cancer. The per-lesion sensitivity, specificity, PPV, NPV,
and accuracy of 18F2/18F-FDG PET/CT, whole-body MRI, bone
scintigraphy, and the combination of whole-body MRI and bone
scintigraphy are shown in Table 4. 18F2/18F-FDG PET/CT had no
statistically significant differences from whole-body MRI in sensitivity (P 5 1.00) or accuracy (P 5 0.56) for extraskeletal lesions.
18F2/18F-FDG PET/CT had significantly higher sensitivity and accuracy for the detection of skeletal lesions than bone scintigraphy
(P , 0.001), but not when compared with whole-body MRI
NUCLEAR MEDICINE • Vol. 56 • No. 12 • December 2015
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FIGURE 1. A 49-y-old woman with breast cancer. (A) Planar whole-body
anterior view from 99mTc-MDP bone scan and (B) maximum-intensityprojection 18F−/18F-FDG PET images show multiple bone metastases,
more conspicuous on PET. (C) Transaxial fused PET/CT scan demonstrates liver metastasis (arrow). (D) Brain metastases are identified on
contrast-enhanced T1-weighted MR images (arrowheads). These were
not seen on 18F−/18F-FDG PET/CT.
(P 5 0.21). 18F2/18F-FDG PET/CT showed no significant differences from the combination of whole-body MRI and bone scintigraphy (P 5 1.00). Overall, 18F2/18F-FDG PET/CT had no
significant differences in sensitivity and accuracy from wholebody MRI (P 5 0.56, P 5 0.17) or the combination of whole-body
MRI and bone scintigraphy (P 5 0.71, P 5 0.74). 18F2/18F-FDG
PET/CT had lower sensitivity and accuracy than a combination of
results from 18F2/18F-FDG PET/CT and whole-body MRI (P ,
0.05). No significant differences in PPV were noted among the 3
examinations.
For osteoblastic lesions, 18F2/18F-FDG PET/CT had significantly higher sensitivity (P , 0.001) and accuracy (P , 0.001)
than bone scintigraphy. 18F2/18F-FDG PET/CT had no statistically
significant differences in sensitivity (P 5 0.21) or accuracy (P 5
0.21) from whole-body MRI. 18F2/18F-FDG PET/CT showed no
statistically significant difference in sensitivity or accuracy from
a combination of whole-body MRI and bone scintigraphy (P 5
1.00, P 5 1.00) or a combination of 18F2/18F-FDG PET/CT and
whole-body MRI (P 5 0.08, P 5 0.08).
Prostate Cancer. The per-lesion sensitivity, specificity, PPV,
NPV, and accuracy of 18F2/18F-FDG PET/CT, whole-body MRI,
bone scintigraphy, and the combination of whole-body MRI and
bone scintigraphy are shown in Table 5. Both 18F2/18F-FDG
PET/CT and whole-body MRI detected additional extraskeletal
lesions in 2 patients. 18F2/18F-FDG PET/CT had significantly
higher sensitivity than whole-body MRI (P , 0.02) and bone scintigraphy (P , 0.03) in the evaluation of skeletal lesions. However,
18F2/18F-FDG PET/CT had no significant difference in sensitivity
from a combination of whole-body MRI and bone scintigraphy
(P 5 0.08). Overall, 18F2/18F-FDG PET/CT had statistically significant higher sensitivity than whole-body MRI (P , 0.02), but not
when compared with a combination of whole-body MRI and bone
scintigraphy (P 5 0.08) or 18F2/18F-FDG PET/CT and whole-body
MRI (P 5 1.00). No statistically significant differences in PPV
were identified between these examinations.
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FIGURE 2. A 70-y-old man with prostate cancer. (A and B) Planar
whole-body anterior view from 99mTc-MDP bone scan (A) and maximumintensity-projection 18F−/18F-FDG PET images (B) show bone metastases
in skull base and right iliac bone, more conspicuous on PET. (C) Skull
base lesion was not identified prospectively on CT or contrast-enhanced
T1-weighted MRI. (D) Right iliac bone lesion was not identified prospectively on CT or contrast-enhanced T1-weighted MRI.
DISCUSSION
Our study suggests that PET/CT done after administration of
and 18F-FDG followed by a single PET/CT scan has
higher accuracy than whole-body MRI and bone scintigraphy
for evaluation of the extent of disease in this population of patients
with breast and prostate cancer. 18F2/18F-FDG PET/CT performed
as well as a combination of whole-body MRI and bone scintigraphy; therefore, it may serve as a one-stop shop in the imaging
management of patients with certain cancers.
Although 18F-FDG PET/CT can provide high diagnostic accuracy
in both the initial and recurrent breast cancer settings compared with
conventional imaging (17–19), it has several limitations for the diagnosis of patients with prostate cancer (5). 18F-FDG PET/CT is also
18F-NaF
FIGURE 3. A 53-y-old woman with breast cancer. (A and B) Planar
whole-body anterior view from 99mTc-MDP bone scan (A) is negative for
bone metastases, whereas maximum-intensity-projection 18F−/18F-FDG
PET images (B) show bone metastases in multiple locations, including
right femur. (C) Proximal right femur metastasis was not identified prospectively on CT or contrast-enhanced T1-weighted MRI. (D) Maximumintensity projection from follow-up 18F−/18F-FDG PET done 6 mo later
demonstrates progression of bone metastases, including in right femur.
BREAST AND PROSTATE CANCER • Minamimoto et al.
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TABLE 2
Results of Per-Patient Analysis
Parameter
Skeletal lesions
Clinical staging
18F−/18F-FDG
Examination
Correct
Overestimate
Underestimate
PET/CT
29 (27)
1 (1)
0 (0)
Whole-body MRI
26
0
0
Bone scintigraphy
28 (26)
0 (0)
2 (2)
Bone scintigraphy 1 whole-body MRI
27
1
0
18F−/18F-FDG
PET/CT 1 whole-body MRI
26
2
0
18F−/18F-FDG
PET/CT
0 (0)
28 (26)
2 (2)
Whole-body MRI
26
2
0
Bone scintigraphy 1 whole-body MRI
26
2
0
18F−/18F-FDG
25
3
0
PET/CT 1 whole-body MRI
Number in parenthesis is result based on 28 patients who had whole-body MRI scan.
not recommended for the detection of osteoblastic skeletal lesions
(3,20). 18F-NaF PET/CT is superior to bone scintigraphy and 18FFDG PET/CT for the detection of osteoblastic metastases (21). Another study showed that whole-body MRI with diffusion-weighted
imaging had results similar to 18F-NaF PET/CT in breast cancer and
superior to bone scintigraphy (22). The combined 18F2/18F-FDG
PET/CT scan can increase sensitivity in the detection of osseous
lesions compared with 18F-FDG PET/CT (14–16,23).
TABLE 3
Per-Lesion Analysis (Breast and Prostate Cancers)
Lesion type
Extraskeletal lesions
Examination
18F−/18F-FDG
PET/CT
Whole-body MRI
Skeletal lesions
18F−/18F-FDG
PET/CT 1 whole-body MRI
18F−/18F-FDG
PET/CT
Osteoblastic lesions
Total lesions
Specificity
PPV
NPV
Accuracy
92.9
0.0
81.3
0.0
76.5
92.9
33.3
86.7
50.0
82.4
82.4
0.0
82.4
NA
96.2*†
33.3
93.7
50.0
89.8‡§
81.4
22.2
89.1
13.3
74.7
Bone scintigraphy
64.6
77.8
96.2
20.0
65.9
Bone scintigraphy 1 whole-body MRI
91.4
22.2
90.1
25.0
83.5
Whole-body MRI
Osteolytic lesions
Sensitivity
100.0
18F−/18F-FDG
PET/CT 1 whole-body MRI
100.0
0.0
89.8
NA
89.8
18F−/18F-FDG
PET/CT
100.0
0.0
83.3
NA
83.3
Whole-body MRI
100.0
0.0
83.3
NA
83.3
Bone scintigraphy
80.0
100.0
100.0
50.0
83.3
Bone scintigraphy 1 whole-body MRI
100.0
0.0
83.3
NA
83.3
18F−/18F-FDG
PET/CT 1 whole-body MRI
100.0
0.0
83.3
NA
83.3
18F−/18F-FDG
PET/CT
95.9*†jj
37.5
93.4
50.0
90.2§¶
Whole-body MRI
80.0
25.0
89.7
13.3
74.0
Bone scintigraphy
63.5
75.0
95.9
18.2
64.6
Bone scintigraphy 1 whole-body MRI
90.8
25.0
90.8
25.0
83.6
90.2
18F−/18F-FDG
PET/CT 1 whole-body MRI
18F−/18F-FDG
PET/CT
0.0
90.2
NA
95.7#
25.0
90.8
42.9
87.6**
Whole-body MRI
83.3
25.0
88.6
17.6
76.0
Bone scintigraphy 1 whole-body MRI
91.6
25.0
89.5
30.0
83.3
100.0
0.0
87.5
NA
87.5
18F−/18F-FDG
PET/CT 1 whole-body MRI
100.0
NA 5 not applicable. 18F−/18F-FDG PET/CT showed significantly higher sensitivity (*P , 0.001,#P , 0.002) and accuracy (‡P , 0.02, **P ,
0.02, ¶P , 0.05) than whole-body MRI. 18F−/18F-FDG PET/CT showed higher sensitivity (†P , 0.001) and accuracy (§P , 0.001) than bone
scintigraphy. 18F−/18F-FDG PET/CT showed lower sensitivity than combination of 18F−/18F-FDG PET/CT and whole-body MRI (jjP 5 0.01).
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TABLE 4
Per-Lesion Analysis (Breast Cancer)
Lesion type
Extraskeletal lesions
Examination
18F−/18F-FDG
Sensitivity
PET/CT
Osteolytic lesions
Osteoblastic lesions
Total lesions
PPV
NPV
Accuracy
78.6
0.0
73.3
91.7
0.0
91.7
33.3
84.6
50.0
80.0
100.0
0.0
80.0
NA
80.0
93.6*
0.0
91.7
0.0
86.3†
Whole-body MRI
85.1
0.0
90.9
0.0
78.4
Bone scintigraphy
53.2
50.0
92.6
8.3
52.9
Bone scintigraphy 1 whole-body MRI
93.6
0.0
91.7
0.0
86.3
Whole-body MRI
Skeletal lesions
Specificity
18F−/18F-FDG
PET/CT 1 whole-body MRI
18F−/18F-FDG
PET/CT
18F−/18F-FDG
PET/CT 1 whole-body MRI
100.0
0.0
92.2
NA
92.2
18F−/18F-FDG
PET/CT
100.0
0.0
83.3
NA
83.3
Whole-body MRI
100.0
0.0
83.3
NA
83.3
Bone scintigraphy
80.0
100.0
100.0
50.0
83.3
Bone scintigraphy 1 whole-body MRI
100.0
0.0
83.3
NA
83.3
18F−/18F-FDG
PET/CT 1 whole-body MRI
100.0
0.0
83.3
NA
83.3
18F−/18F-FDG
PET/CT
0.0
92.9
0.0
86.7‡
92.9*
Whole-body MRI
83.3
0.0
92.1
0.0
77.8
Bone scintigraphy
50.0
33.3
91.3
4.5
48.9
Bone scintigraphy 1 whole-body MRI
92.9
0.0
92.9
0.0
86.7
100.0
0.0
93.3
NA
93.3
93.2‡
0.0
88.7
0.0
83.3§
Whole-body MRI
86.4
14.3
89.5
11.1
78.8
Bone scintigraphy 1 whole-body MRI
93.2
14.3
90.2
20.0
84.8
100.0
0.0
89.4
0.0
89.4
18F−/18F-FDG
PET/CT 1 whole-body MRI
18F−/18F-FDG
PET/CT
18F−/18F-FDG
PET/CT 1 whole-body MRI
NA 5 not applicable. 18F−/18F-FDG PET/CT showed higher sensitivity (*P , 0.001) and accuracy (†P , 0.001) than bone scintigraphy.18F−/18F-FDG PET/CT showed lower sensitivity (‡P , 0.05) and accuracy (§P , 0.05) than combination of results from 18F−/18F-FDG
PET/CT and whole-body MRI.
TABLE 5
Per-Lesion Analysis (Prostate Cancer)
Lesion type
Extraskeletal lesions
Skeletal lesions (osteoblastic)
Examination
18F−/18F-FDG
Sensitivity
PET/CT
PPV
NPV
Accuracy
100.0
100.0
NA
100.0
NA
Whole-body MRI
100.0
NA
100.0
NA
100.0
18F−/18F-FDG
PET/CT 1 whole-body MRI
100.0
NA
100.0
NA
100.0
18F−/18F-FDG
PET/CT
100.0*†
60.0
94.1
100.0
94.6
65.4
40.0
85.0
25.0
61.3
Whole-body MRI
Bone scintigraphy
Total lesions
Specificity
81.3
100.0
100.0
45.5
83.8
Bone scintigraphy 1 whole-body MRI
100.0
40.0
88.5
100.0
89.3
18F−/18F-FDG
PET/CT 1 whole-body MRI
100.0
0.0
82.1
NA
82.1
18F−/18F-FDG
PET/CT
100.0‡
60.0
94.4
100.0
94.9
76.0
40.0
86.4
25.0
70.0
Bone scintigraphy 1 whole-body MRI
100.0
40.0
89.3
100.0
90.0
18F−/18F-FDG
100.0
0.0
83.3
NA
83.3
Whole-body MRI
PET/CT 1 whole-body MRI
NA 5 not applicable. 18F−/18F-FDG PET/CT showed significantly higher sensitivity than whole-body MRI (*P , 0.02) and bone
scintigraphy (†P , 0.03) in evaluation of skeletal lesions. 18F−/18F-FDG PET/CT showed statistically significant higher sensitivity than
whole-body MRI (‡P , 0.02)
IMAGING
OF
BREAST AND PROSTATE CANCER • Minamimoto et al.
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Whole-body MRI detected brain metastases that were missed
on 18F2/18F-FDG PET/CT because of high physiologic 18F-FDG
uptake in the normal cerebral cortex. Therefore, whole-body MRI
may be able to provide complementary information in areas where
18F-FDG PET/CT has known limitations in diagnosis.
Hybrid PET/MRI has recently been introduced clinically. Compared with PET/CT, PET/MRI has advantages due to the better softtissue contrast of MRI (24,25). PET and MRI provide complementary
information, as they evaluate different biologic processes (26).
Therefore, simultaneous 18F2/18F-FDG PET/MRI may provide
more accurate diagnostic performance in patients with breast and
prostate cancer.
Limitations of this study include the relatively small number of
participants, variations in injected dosage, variations in the time
from injection to imaging, and lack of semiquantitative measurements such as SUV. The optimal ratio of 18F-NaF to 18F-FDG in
the 18F2/18F-FDG PET/CT scan is also known to be an issue for
this approach to imaging cancer patients (27).
CONCLUSION
18F2/18F-FDG
PET/CT and whole-body MRI are superior to
scintigraphy for evaluation of the extent of skeletal
disease, as expected from already published data. Further, PET/CT
and whole-body MRI detected extraskeletal disease that may change
the management of these patients. 18F2/18F-FDG PET/CT provides
diagnostic ability similar to that of a combination of whole-body
MRI and bone scintigraphy in patients with breast and prostate cancer. Larger cohorts are needed to confirm these preliminary findings,
ideally using the newly introduced simultaneous PET/MRI scanners.
99mTc-MDP
DISCLOSURE
The costs of publication of this article were defrayed in part by
the payment of page charges. Therefore, and solely to indicate this
fact, this article is hereby marked “advertisement” in accordance
with 18 USC section 1734. GE Healthcare provided financial support for the study; the authors had control of the data and information submitted for publication. No other potential conflict of
interest relevant to this article was reported.
ACKNOWLEDGMENTS
We thank our research coordinators, Frederick Chin, PhD, the
staff at the Lucas Cyclotron, and the technologists in the Division
of Nuclear Medicine and Molecular Imaging. Special thanks are
extended to all our patients and their families.
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NUCLEAR MEDICINE • Vol. 56 • No. 12 • December 2015
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Prospective Comparison of 99mTc-MDP Scintigraphy, Combined 18F-NaF and 18
F-FDG PET/CT, and Whole-Body MRI in Patients with Breast and Prostate Cancer
Ryogo Minamimoto, Andreas Loening, Mehran Jamali, Amir Barkhodari, Camila Mosci, Tatianie Jackson, Piotr Obara,
Valentina Taviani, Sanjiv Sam Gambhir, Shreyas Vasanawala and Andrei Iagaru
J Nucl Med. 2015;56:1862-1868.
Published online: September 24, 2015.
Doi: 10.2967/jnumed.115.162610
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